Tachyphylaxis of the intrinsic cardiac nerves to nicotine: effects on A-V nodal conduction

1. The possibility that responses of the intrinsic cardiac nerves (ICN) of the dog to nicotinic stimulation are influenced by tachyphylaxis to repeated administration of nicotine (NIC) was evaluated in an anaesthetized preparation. Prolongation of A-V conduction was used as an index of ICN responsiveness. 2. Twenty dogs were placed on cardiopulmonary bypass and an electrode was sutured over the His bundle. Both vagi were sectioned, beta-adrenoceptor blockade instituted, and the hearts were paced. Nicotine (2-100 micrograms) was administered directly into the coronary circulation via an aortic catheter. Tachyphylaxis was estimated from the rate of deterioration of negative dromotropic effect of NIC in response to various protocols of repeated doses. 3. Tachyphylaxis was not observed in response to repeated doses of acetylcholine. 4. Tachyphylaxis to nicotine was found to be both time- and dose-dependent; i.e. increasing the dose or decreasing the time between doses to less than 3 min augmented its development. 5. Tachyphylaxis was pronounced after 5 x 100 micrograms doses of NIC, even if the test doses were greater than 3 min apart and 20 min was allowed to elapse between the two series of test doses. 6. These data are descriptive in nature and no mechanism for the tachyphylaxis could be deduced. Pharmacokinetic data of this nature have not been previously reported for nicotinic stimulation of the intrinsic parasympathetic ganglia of the canine heart. Tachyphylaxis can be avoided when testing the intrinsic innervation of the canine heart if the doses used are less than 100 micrograms and are administered at least 3 min apart.